• Title/Summary/Keyword: multiple-RAT

Search Result 178, Processing Time 0.025 seconds

Compositional Change of Hepatic Bile Acid by Multiple Administration of DWP305, a Combined Preparation Containing Ursodeoxycholic Acid and Silymarin, in Rats (흰쥐에서 Ursodeoxycholic Acid 및 Silymarin을 함유한 의약조서울(DWP305)의 연용투여에 의한 간내 담즙산 조성변화)

  • Cho, Jae-Youl;Yeon, Je-Deuk;Nam, Kweon-Ho;Kim, Jeum-Yong;Yoo, Eun-Sook;Yu, Young-Hyo;Park, Myung-Hwan
    • YAKHAK HOEJI
    • /
    • v.40 no.3
    • /
    • pp.311-319
    • /
    • 1996
  • DWP305, a preparation containing combination of ursodeoxycholic acid(UDCA), silymarin and vitamins ($B_1\;and\;B_2$), is a drug currently being developed for hep atic disorders. In order to evaluate the changes in hepatic function by multiple oral administration(2 and 4 weeks) of DWP305 in rats, several biochemical parameters in blood, bile acid composition, and the accumulation of UDCA and lithocholic acid(LCA),a toxic metabolite formed by enterobacteria, were examined using HPLC. In blood biochemical findings, DWP305 did not affect the normal level and there was no difference in total bile acid composition for UDCA, cholic acid(CA), deoxycholic acid(DCA), chenodeoxycholic acid(CDCA) and LCA compared to the UDCA administered group, although total ratio of UDCA and CA was different from normal group. In case of ratio of taurine and glycine conjugated forms, DWP305(186mg/kg as a UDCA) administered group was also similar to normal group and UDCA administered group, while high dosing of DWP305 was not different in the ratio of UDCA administered group(930mg/kg) but normal group. And the ratio of LCA was in order of UDCA(930mg/kg), DWP305(930mg/kg as a UDCA), UDCA(186mg/kg) and DWP305(186mg/kg as a UDCA) administered group, which was less than 4%. The free form of UDCA as well as most of bile acids was not detected at all in rat liver, indicating that there's no accumulation. These results suggest that multiple dosing of DWP305 in rats may not affect hepatic biotransformation and metabolism of bile acids.

  • PDF

Multiple Binding Affinities for Muscarinic Acetylcholine Receptors in Rat Brain (흰쥐 뇌내(腦內)의 무수카린성 콜린 수용체의 이질성(異質性))

  • Lee, Jong-Hwa;El-Fakahany, Esam E.
    • The Korean Journal of Pharmacology
    • /
    • v.23 no.2
    • /
    • pp.101-111
    • /
    • 1987
  • We investigated the binding properties of $(^3H)$ QNB and $(^3H)$ NMS to mAchR to elucidate the characterstics of mAchR in rat brain by using two different preparations (homogemates & intact brain cell aggregates). The binding properties of both ligands demonstrated high affinity and saturability in both experiments, however $(^3H)$ QNB showed a significantly higher maximal binding capacity than tha ot $(^3H)$ NMS 1. In rat brain homogenates; Displacement of both lignands with several mAchR antagonists resulted in competition curves in accoradnce with the law of massaction for QNB, atropine & scopolamine in thie preparation, also a similar profile was found for the quaternary ammonium analogs of atropine & scopolamine (methyl atropine & methylscopolamine) when $(^3H)$ NMS was used to label the receptors in rat brain. But when these hydrophillic antagonists were used to displace $(^3H)$ QNB, they showed interaction with high- and low-affinity binding sites in brain homogenates. Pirenzepine, the nonclassical mAchR antagonist, was able to displace both ligands from binding sites in this preparation. 2. In intact rat brain cell aggregates; Intact bain cell aggregates were used to elucidate the binding characteristics of $(^3H)$ NMS to mAchR in rat. The magnitude of binding of this ligand was related linearly to the amount of cell protein in the binding assay with a high ratio of total to nonspecific binding. mAchR antagonists displaced specific $(^3H)$ NMS binding according to the law of mass-action, while it was possible to resolve displacement curves using mAchR agonist into high-& low-affinity component. 3. Our results indicate that more hydrophilic receptor ligand $(^3H)$ QNB, displacement experiments in both tissues demonstrated that the lipid solubility of a particulr mAchR ligand might play an important role in determining its profile of binding to the mAchR, and the concentrations of mAchR in rat brain are both on the cell surface (membrane-bound receptor) and in the intracelluar membrane (intermembrane-bound receptor). 4. The results are discussed in terms of the usefulness of dissociated intact rat brain cells in studying mAchR in central nervous system.

  • PDF

Body Distribution of $^{125}I-rhEGF$ Across Normal and Damaged Rat Skins (정상 및 손상된 흰쥐 피부에 국소 적용된 $^{125}I-rhEGF$의 체내 이행)

  • Lee, Jeong-Uk;Chung, Suk-Jae;Lee, Min-Hwa;Shim, Chang-Koo
    • YAKHAK HOEJI
    • /
    • v.41 no.6
    • /
    • pp.730-736
    • /
    • 1997
  • Distribution of radioactivity in the skin tissues, subcutaneous tissues, blood and body organs was examined following topical application of $^{125}I-rhEGF$(0.4 ${\mu}Ci$), in the form of a Pluronic F-127 gel, on the normal and damaged (burned and stripped) skins of SD male rats. The radioactivity in the skin tissues and subcutaneous tissues was 3-5 times higher for the damaged skins than for the normal skin. But pretreatment of the skin with rhEGF (1${\mu}g$)) twice at 24 hr dose intervals affected the distribution of the radioactivity yielding the order of burned skin> stripped skin=normal skin. The decrease for the stripped skin by the pretreatment might be related either to the pathophysiological change of the skin or to the down regulation of the EGF receptor. Liver showed the highest radioactivity in amount following single and multiple administration of the drug to the normal and damaged skins. But,in concentration, the kidney and stomach showed higher value than the liver which is consistent with that kidney is a major eliminating organ of EGF and that EGF exerts its pharmacological effect specifically for the stomach.

  • PDF

Analysis of Massive MIMO Wireless Channel Characteristics (Massive MIMO 시스템의 무선 채널 특성 분석)

  • Jang, Jeong-Uk;Kim, Jin-Hyuk;Mun, Cheol
    • The Journal of Korean Institute of Communications and Information Sciences
    • /
    • v.38B no.3
    • /
    • pp.216-221
    • /
    • 2013
  • In this paper, wireless channel characteristics of massive MIMO system is analyzed by comparing angular spread, cross polarization discrimination(XPD) and delay spread of dual polarized 4 and 128 transmit array antenna systems, by using 3D rat-tracing simulator, Wireless Insite in microcell environments. The analysis shows that increasing the number of transmit antennas results in the smaller angular spread and delay spread, and the higher value of XPD.

Curcumin modulates the apolipoprotein B mRNA editing by coordinating the expression of cytidine deamination to uridine editosome components in primary mouse hepatocytes

  • He, Pan;Tian, Nan
    • The Korean Journal of Physiology and Pharmacology
    • /
    • v.23 no.3
    • /
    • pp.181-189
    • /
    • 2019
  • Curcumin, an active ingredient of Curcuma longa L., can reduce the concentration of low-density lipoproteins in plasma, in different ways. We had first reported that curcumin exhibits hypocholesterolemic properties by improving the apolipoprotein B (apoB) mRNA editing in primary rat hepatocytes. However, the role of curcumin in the regulation of apoB mRNA editing is not clear. Thus, we investigated the effect of curcumin on the expression of multiple editing components of apoB mRNA cytidine deamination to uridine (C-to-U) editosome. Our results demonstrated that treatment with $50{\mu}M$ curcumin markedly increased the amount of edited apoB mRNA in primary mouse hepatocytes from 5.13%-8.05% to 27.63%-35.61%, and significantly elevated the levels of the core components apoB editing catalytic polypeptide-1 (APOBEC-1), apobec-1 complementation factor (ACF), and RNA-binding-motif-protein-47 (RBM47), as well as suppressed the level of the inhibitory component glycine-arginine-tyrosine-rich RNA binding protein. Moreover, the increased apoB RNA editing by $50{\mu}M$ curcumin was significantly reduced by siRNA-mediated APOBEC-1, ACF, and RBM47 knockdown. These findings suggest that curcumin modulates apoB mRNA editing by coordinating the multiple editing components of the edito-some in primary hepatocytes. Our data provided evidence for curcumin to be used therapeutically to prevent atherosclerosis.

Hypoxia Induced Expression of Vascular Endothelial Growth Factor in Rat Pulmonary Artery Smooth Muscle Cells (쥐의 폐동맥 평활근 세포에서 저산소에 의한 Vascular Endothelial Growth Factor의 발현)

  • Nho, Un Seok;Kim, Yeo Hyang;Hyun, Myung Chul;Lee, Sang Bum
    • Clinical and Experimental Pediatrics
    • /
    • v.46 no.2
    • /
    • pp.167-172
    • /
    • 2003
  • Purpose : Pulmonary vascular hypertension is a common problem in congenital heart disease, the most common cardiac condition in childhood. However, the mechanisms responsible for this pathologic change, treatment, and prevention are poorly understood. Therefore, we studied the gene expression of vascular endothelial growth factor(VEGF) by using a hypoxic model of the pulmonary artery smooth muscle cells. Methods : The main pulmonary artery and its proximal branches of a 6 wk old Fischer rat were excised. They were cut into multiple small pieces and suspended in DMEM medium supplemented with 20% fetal bovine serum and incubated in 5% $CO_2$-95% air atmosphere. The smooth muscle cells were confirmed by immunostaining with smooth muscle myosin and ${\alpha}$-smooth muscle actin antibodies. The VEGF gene expression in the hypoxic group was compared with the one in control the group as well as the one in the starved group by RT-PCR and Northern blot hybridization. Results : There was no statistically significant difference among the control, hypoxic and starved groups. Conclusion : There are few studies of pulmonary vascular hypertension at the molecular level in Korea. Therefore, we studied the expression of VEGF gene in hypoxic pulmonary vascular smooth muscle cells. Further studies will be needed to find the difference between newly born and adult rats, or human and rat pulmonary vascular smooth muscle cells in gene expression. We hope that the study will lead to a better understanding of pulmonary vascular hypertension.

Interleukin-$1{\beta}$ induces bone resorption by regulation of prostaglandin $E_2$ synthesis and plasminogen activator activity, and TGF-$\beta$ inhibits bone resorption of rat bone cells (쥐의 골세포에서 $PGE_2$ 합성과 plasminogen activator 활성 조절에 의한 IL-$1{\beta}$의 골 흡수유도와 TGF-$\beta$에 의한 골 흡수 억제 기전에 관한 연구)

  • Kim, Young-Hun;Lee, Young-Jun;Chung, Kyu-Rhim;Park, Young-Guk
    • The korean journal of orthodontics
    • /
    • v.30 no.6 s.83
    • /
    • pp.713-721
    • /
    • 2000
  • Bone cells produce multiple growth factors and cytokines that have effects on bone metabolism and can be incorporated into the bone matrix. The present study was designed to extend these observations by examining the interactions between transforming growth factor-$\beta$(TGF-$\beta$) or interleukin-$1\beta$(rhIL-$1\beta$) and bone cells in a rat long bone culture model. IL-$1\beta$ regulates several activities of the osteoblast cells derived from rat long bone explants in vitro. IL-$1\beta$ stimulated cellular proliferation as well as the synthesis of prostaglandin $E_2$ and Plasminogen activator activity in the cultured cells in a dose-dependent manner. TGF-$\beta$ is present in the bone matrix and potentially released during bone resorption. TGF-$\beta$ reduced basal bone resorption and inhibited vitamin $D_3[1,25(OH)_2D_3]$-induced bone resorption in rat long bone cells. These results support the role of IL-$1\beta$ in the pathological modulation of bone cell metabolism, with regard to implication in the Pathogenesis of osteoporosis by IL-$1\beta$, and that TGF-$\beta$ positively inhibits the bone resorption.

  • PDF

BQ-123, $ET_{A}$ antagonist, decreases clinical sign and inflammatory region on EAE.

  • Kang, Bong-Su;Park, Young-Shim;In hoi Huh
    • Proceedings of the Korean Society of Applied Pharmacology
    • /
    • 1996.04a
    • /
    • pp.191-191
    • /
    • 1996
  • BQ-123, a selective $ET_{A}$ receptor antagonist, reverses various responses induced by Endothelin-1 and it has been reported that BQ-123 ameliorates the cerebrovascular constriction, hypertension, and decrease of blood flow. Previously, we announced that the level of Endothelin-2 increase in the brain and spinal cord of EAE-induced lewis rat and showed the origin of ET-1 is activated macrophages. Intracisternal injection of $ET_{A}$ receptor antagonist, BQ-123(10nmol) was done for visualizing the role of endothelin-1 on the pathogenesis of EAE. BQ-123 apparently blocked the severity of clinical score of EAE and decreased the histologically observed inflammatory region. The blocking effect on the progression of EAE model following BQ-123, suggests that BQ-123 is a physiological antagonist in terms of development of the sign of multiple sclerosis.

  • PDF

The Effect of Phosphodiesterase-4-Specific Inhibitor in the Rat Model of Spinal Nerve Ligation

  • Kim, Sung-Hoon;Park, Bit-Na-Ri;Kim, Seok-Won
    • Journal of Korean Neurosurgical Society
    • /
    • v.50 no.2
    • /
    • pp.109-113
    • /
    • 2011
  • Objective : Peripheral neuropathy is characterized by hyperalgesia, spontaneous burning pain, and allodynia. The purpose of this study was to investigate the effect of rolipram, a phosphodiesterase-4-specific inhibitor, in a segmental spinal nerve ligation model in rats. Methods : Both the L5 and L6 spinal nerves of the left side of the rats were ligated. Phosphodiesterase-4 inhibitor (rolipram) and saline (vehicle) were administered intraperitoneally. We measured mechanical allodynia using von Frey filaments and a nerve conduction study. Results : The mechanical allodynia, which began to manifest on the first day, peaked within 2 days. Multiple intraperitoneal injections of rolipram ameliorated the mechanical allodynia. Furthermore, an intraperitoneal administration of rolipram improved the development of pain behavior and nerve conduction velocity. Conclusion : This study suggests that the phosphodiesterase-4 inhibitor, rolipram, alleviates mechanical allodynia induced by segmental spinal nerve ligation in rats. This finding may have clinical implications.

Strain-specific mammary tumor development following life-time oral administration of Ochratoxin A in DA and Lewis rats

  • Son, Woo-Chan;Lee, Yong-Soon;Kang, Kyung-Sun
    • Proceedings of the Korean Society of Toxicology Conference
    • /
    • 2003.05a
    • /
    • pp.39-40
    • /
    • 2003
  • Ochratoxin A (OA), a potent nephrotoxin in several species, is knownto be a renal carcinogen in animals and is implicated in the etiology of Balkan endemic nephropathy (BEN). The NTP (National Toxicology Program) classified Ochratoxin A as having clear evidence of carcinogenic activity, based on uncommon tubular adenomas and tubular cell carcinomas of the kidney and multiple fibroadenomas of the mammary gland, seen in the rat.(omitted)

  • PDF